Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation

Author:

Rosen Roni1,Quezada-Diaz Felipe F.1ORCID,Gönen Mithat2,Karagkounis Georgios1ORCID,Widmar Maria1,Wei Iris H.1,Smith J. Joshua1ORCID,Nash Garrett M.1,Weiser Martin R.1ORCID,Paty Philip B.1,Cercek Andrea3,Romesser Paul B.4ORCID,Sanchez-Vega Francisco5ORCID,Adileh Mohammad1,Roth O’Brien Diana4,Hajj Carla4,Williams Vonetta M.4,Shcherba Marina3,Gu Ping3,Crane Christopher4,Saltz Leonard B.3,Garcia Aguilar Julio1ORCID,Pappou Emmanouil1ORCID

Affiliation:

1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

3. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

4. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

5. Department of Computational Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA

Abstract

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan–Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11–47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5–66.5%), 54.5% (95% CI 44.4–66.8%), and 26.8% (95% CI 18.6–38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16–46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99–42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05–6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Funder

National Institutes of Health/National Cancer Institute (NIH/NCI) Memorial Sloan Kettering Cancer Center

Publisher

MDPI AG

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